Iron in HEALTH and DISEASE Flashcards
Where is iron present?
- Hb
- Myoglobin
- enzymes (cytochromes)
Why is iron dangerous?
chemical reactivity
(may cause Oxidative stress and free radical prdn)
—-should be transported, stored SAFELY
Can the body excrete iron?
NO
Where is MAJORITY of the body’s iron found?
In the haem
- Fe2+ ion sits in PROPHYRIN ring
How much iron is lost every day?
1 mg
loss d.t loss of cells –bleeding, mucosal cells
How much serum iron at any given time?
4 mg
Where is iron absorbed?
- in DUODENUM
- —by duodenal mucosa
Which iron is readily absorbed?
- HAEM-IRON
What enhances iron absorption?
- ascorbic acid (reduces IRON to FE2+)
- alcohol
what inhibits iron absorption?
- Tannins (TEA)
- pHYTATES (CEREALS/ BRAN, NUTS AND SEEDS)
- calcium (dairy products
WHat is involved in IRON absorption?
- duodenal cytochrome B in the luminal surface (converts FERRIC 3+ iron to FERROUS iron)
- DMT-1 transports ferrous iron INTO the duodenal enterocyte
- Ferroportin (exports iron FROM the enterocyte—to transferin for transport)
What regulates iron absorption?
HEPCIDIN (produced in the liver)
—-incr. in response to INCR. IRON load and inflammation (malignancy)
What is MOA of hepcidin>
- BINDS to ferroportin and CAUSES its DEGEN.
- –so iron is TRAPPED in duodenal cells and macrophages
What occurs to hepcidin levels when iron is deficient?
- DECREASES
How to assess iron status? (3 compartments)
- Functional Iron (Hb conc.)
- Transport iron/ IRON supply to tissues (% saturation of TRANSFERRIN)
- Storage iron (serum FERRITIN/ tissue biopsy- rare)
What is transferrin?
- transports iron from DONOR tissues (macrophages/ intestinal and liver cells) to the tissues EXPRESSING transferrin receptors
- —-ALLOWS the SAFE transport of iron
What tissue is rich in transferrin receptors?
- erythroid marrow (cells )
What is transferrin saturation?
- measures IRON SUPPLY
- —serum iron/ total iron binding capacity (to transferrin) x 100%
What occurs in iron overload?
- transport system is compromised
- –transferrin saturation is 100%
What does transferrin saturation reflect?
- the proportion of diferric transferrin
HIGH affinity for cellular transferrin receptors
What does a small level of serum ferritin indicate?
- indirect measure of STORAGE iron
- –reflects intracellular ferritin synthesis
When may ferritin serum levels go up?
- with INFECTION and malignancy
it’s an ACUTE phase protein
When is it best to look at ferritin levels?
- for IRON deficiency.
What does it mean by negative iron balance?
losing iron more than you are absorbing
What are the consequences of NEGATIVE iron balance?
- exhaustion of iron stores
- iron deficient erythropoiesis
* FALLING MCV) - Microcytic anaemia
- Epithelial changes (Skin/ koilonychia/ angular stomatitis)
What does hypochromic and microcytic anaemia indicte?
DEFICIENT Hb synthesis
What 2 parameters to CONFIRM dx of iron deficiency>
- Decr. Hb iron
- Reduced STORAGE iron (FERRITIN)
What causes iron def.?
- more likely women and children
- vegetarian
- too much bleeding
- not absorbing enough (CELIAC disease)
What are chronic causes of blood loss?
- menorrhagia
- GI (tumors/ ulcer/ NSAIDs/ parasitic infection)
- Hematuria
What is meant by OCCULT blood loss?
- GI blood loss of 8-10 ml per day (tsp)–4-5 mg of iRON
- —–MAX iron absorption is 4-5mg; negative iron balance may occur
What is iron malutilisation?
- anaemia of chronic disease
Where is iron malutilisation commonly seen?
in hospitalized pts
Why is iron def. seen in chronic disease pts?
d.t INFLAMMATORY macrophage IRON block —- Body’s reaction in making iron LESS available to the pathogen
How does the inflammatory rxn result in IRON block?
Increased transcription of ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increased
Increased plasma hepcidin blocks ferroportin-mediated release of iron
Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells
What occurs in Hereditary hemochromatosis?
- mutation in HFE gene
- —–decr. SYNTHESIS of HEPCIDIN
- —-incr. iron absorption —-eventual iron accumulation and RISK of END-ORGAN damage.
How does hereditary hemochromatosis present as?
- fatigue
- JOINT pain
- IMPOTENCE
- arthritis
- CIRRHOSIS
- DIABETES
- cardiomyopathy
How to dx Hereditary hemochromatosis?
- transferin sat. >50%
- —incr. iron stores (serum ferritin >300in men and >200microgrma/l in pre-menopausal women)
How to confirm dx of HHC?
0 LIVER biopsy
—-FIBROSCAN available to assess cirrhosis
How to TREAT Hereditary hemochromatosis?
WEEKLY VENESECTION (450-500ml) ----intial aim to EXHAUST iron stores (<20 mcg/L ferritin) ---maintain at 50 mcg/L after
chance of a first degree relative having hereditary hemochromatosis?
First degree relative of cases (esp. in SIBLINGS) - 1 in 4 chance !
—-kids WAIT until they are adults; for informed consent
Is haemochromatosis asymptomatic?
YES until irreversible organ damage OCCURS
What are the sources of iron-loading anaemias?
- repeated red cell transfusions
- excessive IRON absorption related over erythropoiesis
What disorders cause iron loading anemias?
(anaemia in the presence of HIGH serum ferritin/ transferrin)
- massive ineffective erythropoiesis (Thalassaemia and Sideroblastic anaemias)
- refractory hypoplastic anaemias (red cell APLASIA and MYELODYSPLASIA)
What refractory hypoplastic anaemias cause iron-loading anaemias?
red cell aplasia
myelodysplasia
Explain the consequence of iron loading.
red cell transfusion and incr. iron absorption–> IRON OVERLOAD–> DAMAGE TO LIVER, HEART AND ENDOCRINE glands
How to treat IIary iron overload?
—-IRON chelating agents (DESFERROIOXAMINE–S/c or Iv)
- –desferipone
- -deferasirox
Why is venesection not ideal in IIaryiron overload?
— not ideal to perform on an already ANEMIC pt
What is seen in Sideroblastic anaemia?
- EXCESS iron build up in MITOCHONDRIA (failure to incorp/ iron in to haem)
Why is iron essential?
- oxygen transport
- electron transport (mitochondrial prodn of ATP)
